Assessment of monoclonal antibodies anti-SARS-CoV-2 with broadly neutralizing capacity obtained by Phage Display

• Grant number: 24/15782-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 01, 2025
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Carlos Roberto Prudencio
• Grantee: Hernan Hermes Monteiro da Costa
• Supervisor: Florian Krammer
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Icahn School of Medicine at Mount Sinai, United States
• Associated to the scholarship: 22/05566-1 - Construction and selection of a library of scFv monoclonal antibodies against the SARS-CoV-2 spike protein by Phage Display technology, BP.DR

Abstract

Most current therapeutic antibodies for COVID-19 were developed to the Spike protein of SARS-CoV-2. However, their effectiveness has been diminished due to antigenic variation, driven mainly by mutations in the receptor-binding domain (RBD) of the Spike protein, highlighting the need of searching for broadly neutralizing antibodies that can target both existing and future variants. In this context, the fusion peptide (FP), an extremely conserved region among SARS-CoV-2 variants and essential for the viral entry process, might represents a critical target for therapeutic and preventive measures against SARS-CoV-2. The primary objective of this project is to develop broadly neutralizing monoclonal antibodies (bnAbs) that target the main variants of concern (VOCs) of SARS-CoV-2. These antibodies can be utilized in both immunotherapy and preventive strategies to enhance protection against COVID-19 across different viral variants. The bnAbs were selected from a hyperimmune library of single-chain antibody fragments by Phage Display, constructed from a cohort of infected and/or vaccinated individuals of the Institute Emilio Ribas of Infectious Disease and Institute Adolfo Lutz, São Paulo, Brazil. Our biopanning strategy was focused on the FP, and the most reactive antibodies with potential for neutralization activity will be expressed in the scFv-Fc format in mammalian cells, purified by protein G chromatography and subsequently tested for their functional neutralizing capabilities. Therefore, the aim of this proposal is to characterize the neutralizing efficacy of the bnAbs against the main VOCs, using microneutralization assays, complementing studies made in Brazil. These activities will be conducted at the Icahn School of Medicine at Mount Sinai (New York, USA), under Dr. Florian Krammer supervision. The project involves applying for a research-abroad internship grant (BEPE) as part of the ongoing PhD (FAPESP No. 2022/05566-1). The products may be translated through the Center for Translational Science and Biopharmaceutical Development (FAPESP No. 21/11936-3).